Research Proposal: Introduction of antigenically diverse populations of hemoparasites in previously infected or immunized individuals permits clinical disease through evasion of host immunity. Limited information is currently available on the contribution of the arthropod phase of the lifecycle, especially in ticks, to the antigenic diversity of hemoparasites. Antigenic diversity created during this phase may be largely responsible for the variability observed in many surface proteins. The research proposed herein aims to determine whether the vector influences antigenic diversification, by what mechanisms these changes occur, and how this diversity affects immunologically relevant epitopes. The hemoparasite model we will use for this research is infection of cattle with Babesia bovis. For B. bovis, merozoite surface antigen2 (msa-2) genes from vaccine breakthrough isolates examined are significantly different from the msa-2 genes of the vaccine strains used to immunize these animals. This finding strongly suggests that changes in these genes may contribute to immune system evasion. Two hypotheses will be tested. The first is that the generation of nucleotide variation in the msa-2a and -2b genes of B. bovis occurs within the tick vector. The second is that msa-2a and -2b genes among distinct strains of B. bovis encode strain-specific inhibition-sensitive B-cell epitopes. Understanding how, when, and where antigenic diversity is generated will address a major gap in our knowledge regarding protective immunity and breakthroughs in vaccinated or previously infected individuals. The Candidate: The candidate is a veterinarian completing a residency in comparative anatomic pathology and a Ph.D. degree. The candidate has fulfilled most of the requirements of his pathology training along with all didactic course work and his candidacy exam, and is actively pursuing the research portion of his training. This research proposal constitutes his plan to investigate immunologic mechanisms of hemoparasitic infection. Environment: The Department of Veterinary Microbiology and Pathology at Washington State University provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education, residency programs, and extensive collaboration both within and outside the university. The sponsors collaborate closely in research and have successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.